Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT.

To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the femoral artery and hepatic vein by means of the hepatic catheterization technique. Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22 in control and 79 +/- 13 in diabetic subjects, P </= 0.01), whereas early phase secretion was impaired in diabetes. We also measured hepatic insulin extraction (higher in diabetic than in control subjects, P = 0.03) and insulin clearance. The measured data were also used to validate a previously proposed mathematical model, developed to quantify prehepatic secretion, hepatic insulin extraction, and insulin clearance during OGTT, when C-peptide and insulin concentrations are systemically measured. We found good correspondence between experimental data and model estimates for prehepatic insulin secretion (P > 0.3, r(2) = 0.93), whereas estimation of hepatic insulin extraction and insulin clearance needs further investigation for improvement.

[1]  C Cobelli,et al.  The kinetics of insulin in man. I. General aspects. , 1987, Diabetes/metabolism reviews.

[2]  E. Ferrannini,et al.  Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin. , 1978, The Journal of clinical investigation.

[3]  R. Bergman,et al.  Calculated Pattern of Intraportal Insulin Appearance Without Independent Assessment of C-Peptide Kinetics , 1987, Diabetes.

[4]  M Berman,et al.  A model of the kinetics of insulin in man. , 1974, The Journal of clinical investigation.

[5]  B. Desbuquois,et al.  Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. , 1971, The Journal of clinical endocrinology and metabolism.

[6]  C Cobelli,et al.  Insulin Secretion and Hepatic Extraction in Humans by Minimal Modeling of C-Peptide and Insulin Kinetics , 1988, Diabetes.

[7]  L. Rowell,et al.  INDOCYANINE GREEN CLEARANCE AND ESTIMATED HEPATIC BLOOD FLOW DURING MILD TO MAXIMAL EXERCISE IN UPRIGHT MAN. , 1964, The Journal of clinical investigation.

[8]  K Thomaseth,et al.  Integrated mathematical model to assess beta-cell activity during the oral glucose test. , 1996, The American journal of physiology.

[9]  G Pacini,et al.  Mathematical models of insulin secretion in physiological and clinical investigations. , 1994, Computer methods and programs in biomedicine.

[10]  J. Tobin,et al.  Kinetics of Native Insulin in Diabetic, Obese, and Aged Men , 1979, Diabetes.

[11]  F. Féry,et al.  Glucose Metabolism During the Starved-To-Fed Transition in Obese Patients With NIDDM , 1994, Diabetes.

[12]  H. Kuzuya,et al.  Characterization of Seven C-peptide Antisera , 1978, Diabetes.

[13]  Claudio Cobelli,et al.  Physiologic Evaluation of Factors Controlling , 1981 .

[14]  K Thomaseth,et al.  PANSYM: a symbolic equation generator for mathematical modelling, analysis and control of metabolic and pharmacokinetic systems. , 1994, Computer methods and programs in biomedicine.

[15]  G. Pacini,et al.  Intravenous calcitriol normalizes insulin sensitivity in uremic patients. , 1995, Kidney international.

[16]  G. Pacini,et al.  Beta-cell activity and hepatic insulin extraction following dexamethasone administration in healthy subjects. , 1996, Metabolism: clinical and experimental.

[17]  Bruce H. Frank,et al.  Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. , 1986, The Journal of clinical investigation.

[18]  M Weissel,et al.  Elevated hepatic insulin extraction in essential hypertension. , 1993, Hypertension.

[19]  D. Steiner,et al.  The metabolism of proinsulin and insulin by the liver. , 1972, The Journal of clinical investigation.

[20]  G. Pacini,et al.  Elevated Islet Amyloid Pancreatic Polypeptide and Proinsulin in Lean Gestational Diabetes , 1997, Diabetes.

[21]  G Pacini,et al.  Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects. , 1992, Metabolism: clinical and experimental.

[22]  S. Gasic,et al.  Contribution of Splanchnic and Peripheral Vascular Tissues to the Disposal of Angiotensin‐II and to Regional Conversion Rates of Angiotensin‐I: A Pilot Study in Humans , 1991, Journal of cardiovascular pharmacology.

[23]  G. Pacini,et al.  Amylin Release During Oral Glucose Tolerance Test , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[24]  Jeppe Sturis,et al.  Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance , 1992, Diabetes.

[25]  Carl de Boor,et al.  A Practical Guide to Splines , 1978, Applied Mathematical Sciences.